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Waxman S, Brazile BL, Yang B, Lee P-Y, Hua Y, Gogola AL, Lam P, Voorhees AP, Rizzo JF, Jakobs TC, Sigal IA. Lamina cribrosa vessel and collagen beam networks are distinct. Exp Eye Res 2021;:108916.Abstract
Our goal was to analyze the spatial interrelation between vascular and collagen networks in the lamina cribrosa (LC). Specifically, we quantified the percentages of collagen beams with/without vessels and of vessels inside/outside of collagen beams. To do this, the vasculature of six normal monkey eyes was labeled by perfusion post-mortem. After enucleation, coronal cryosections through the LC were imaged using fluorescence and polarized light microscopy to visualize the blood vessels and collagen beams, respectively. The images were registered to form 3D volumes. Beams and vessels were segmented, and their spatial interrelationship was quantified in 3D. We found that 22% of the beams contained a vessel (range 14%-32%), and 21% of vessels were outside beams (13%-36%). Stated differently, 78% of beams did not contain a vessel (68%-86%), and 79% of vessels were inside a beam (64%-87%). Individual monkeys differed significantly in the fraction of vessels outside beams (p < 0.01 by linear mixed effect analysis), but not in the fraction of beams with vessels (p > 0.05). There were no significant differences between contralateral eyes in the percent of beams with vessels and of vessels outside beams (p > 0.05). Our results show that the vascular and collagenous networks of the LC in monkey are clearly distinct, and the historical notions that each LC beam contains a vessel and all vessels are within beams are inaccurate. We postulate that vessels outside beams may be relatively more vulnerable to mechanical compression by elevated IOP than are vessels shielded inside of beams.
Hennein L, Robbins SL. Thyroid-Associated Orbitopathy: Management and Treatment. J Binocul Vis Ocul Motil 2021;:1-15.Abstract
Thyroid-associated orbitopathy (TAO) is a leading cause of orbital and strabismus symptoms in adults. Over the last decade, new treatments have greatly changed available options to alleviate symptoms and improve outcomes. This article discusses the pathophysiology and natural disease course of TAO, including when to pursue urgent treatment and when to consider other diagnoses. This article highlights the interventions that may alter the disease course and offers a comprehensive review on evidence-based interventions for both supportive therapy and systemic agents. The surgical strategies and principles for the treatment of TAO are discussed, including indications for combined surgical interventions and varying surgical techniques.
Habib LA, Yoon MK. Patient specific implants in orbital reconstruction: A pilot study. Am J Ophthalmol Case Rep 2021;24:101222.Abstract
Purpose: Successful repair of the orbital skeleton restores function and cosmesis by normalizing globe position and allowing full motility of the extraocular muscles. Routine repairs are successful with standard implants. However, defects that are irregular or cause volume deficiency can be challenging to repair. The development of patient specific implants (PSI) offers an additional tool in complex cases. Herein, we report our experience using PSI for orbital reconstruction. Methods: An IRB-approved review was conducted of consecutive patients who received PSI from 8/2016-9/2018. Demographic and examination findings were recorded. PSI was designed using high-density porous polyethylene or polyetheretherketone (PEEK) and implanted for repair. The postoperative course was reviewed for outcomes and complications. Results: Eight patients were identified. Two had silent sinus syndrome, 3 were complex facial fracture revisions, and 3 were post-oncologic reconstruction. Seven received porous polyethylene implants, and 1 had a PEEK implant. Mean follow up time was 10.2 months (3.3-28.3). All had an improved functional and aesthetic result. Diplopia and enophthalmos completely resolved in 60% of fracture and silent sinus patients. All fracture and silent sinus patients were orthotropic without diplopia in primary gaze at last follow up. Tumor patients had improvement in symmetry and functionality. There were no complications. Conclusion and importance: Complex orbital skeleton derangements can be difficult to repair and standard implants may incompletely resolve the anatomic problem. In challenging cases, PSI may better achieve an aesthetically and anatomically successful outcome and improve functionality.
Sobel RK, Aakalu VK, Vagefi RM, Foster JA, Tao JP, Freitag SK, Wladis EJ, McCulley TJ, Yen MT. Orbital Radiation for Thyroid Eye Disease: A Report by the American Academy of Ophthalmology. Ophthalmology 2021;Abstract
PURPOSE: To review the current literature on the safety and efficacy of orbital radiation for the management of thyroid eye disease (TED). METHODS: A literature search was conducted last in February 2021 of the PubMed database to identify all articles published in the English language on original research that assessed the effect of orbital radiation on TED. The search identified 55 articles, and 18 met the inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study, and all of them were rated level III. RESULTS: Two large retrospective studies demonstrated the efficacy of radiation treatment, with or without corticosteroid use, in preventing or treating compressive optic neuropathy (CON). Three studies highlighted the role of orbital radiation therapy (RT) to facilitate the tapering of corticosteroids. Several other studies showed a possible role for RT to improve diplopia and soft tissue signs. CONCLUSIONS: Although no level I or level II evidence exists, the best available evidence suggests that orbital radiation, used with or without corticosteroids, is efficacious in preventing CON, improving motility restriction, and decreasing clinical activity in TED. Orbital radiation also may facilitate a corticosteroid taper. Together, these studies show that RT seems to modify the active phase of TED. Short-term risks of orbital radiation are minor, but long-term outcome data are lacking.
Collantes ERA, Delfin MS, Fan BJ, Torregosa JMR, Siguan-Bell C, de Florcruz NVG, Martinez JMD, Masna-Hidalgo BJ, Guzman VPT, Anotado-Flores JF, Levina FD, Hernandez SRC, Collantes AA, Sibulo MC, Rong SS, Wiggs JL. EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma. Hum Mutat 2021;Abstract
Juvenile open-angle glaucoma (JOAG) is a severe type of glaucoma with onset before age 40 and dominant inheritance. Using exome sequencing we identified 3 independent families from the Philippines with novel EFEMP1 variants (c.238A>T, p.Asn80Tyr; c.1480T>C, p.Ter494Glnext*29; and c.1429C>T, p.Arg477Cys) co-segregating with disease. Affected variant carriers (N = 34) exhibited severe disease with average age of onset of 16 years and with 76% developing blindness. To investigate functional effects, we transfected COS7 cells with vectors expressing the three novel EFEMP1 variants and showed that all three variants found in JOAG patients caused significant intracellular protein aggregation and retention compared to wild type and also compared to EFEMP1 variants associated with other ocular phenotypes including an early-onset form of macular degeneration, Malattia Leventinese/Doyne's Honeycomb retinal dystrophy. These results suggest that rare EFEMP1 coding variants can cause JOAG through a mechanism involving protein aggregation and retention, and that the extent of intracellular retention correlates with disease phenotype. This is the first report of EFEMP1 variants causing JOAG, expanding the EFEMP1 disease spectrum. Our results suggest that EFEMP1 mutations appear to be a relatively common cause of JOAG in Filipino families, an ethnically diverse population.
Azad AD, Chandramohan A, Li AS, Rosenblatt TR, Reeves M-GR, Pasricha MV, Ludwig CA, Nguyen A, Winges KM, Wang SY, Pan CK, Moss HE, Do DV, Fountain TR, Kossler AL. Representation of Women in Ophthalmology Subspecialty Societies over 20 Years. Ophthalmology 2021;Abstract
The representation of women has increased over the last 20 years among ophthalmology subspecialty society new membership, award winners, and executive committee membership; however, proportional representation is still lacking at most benchmarks.
Chang W-C, Abe R, Anderson P, Anderson W, Ardern-Jones MR, Beachkofsky TM, Bellón T, Biala AK, Bouchard C, Cavalleri GL, Chapman N, Chodosh J, Choi HK, Cibotti RR, Divito SJ, Dewar K, Dehaeck U, Etminan M, Forbes D, Fuchs E, Goldman JL, Holmes JH, Hope EA, Hung S-I, Hsieh C-L, Iovieno A, Jagdeo J, Kim MK, Koelle DM, Lacouture ME, Le Pallec S, Lehloenya RJ, Lim R, Lowe A, McCawley J, McCawley J, Micheletti RG, Mockenhaupt M, Niemeyer K, Norcross MA, Oboh D, Olteanu C, Pasieka HB, Peter J, Pirmohamed M, Rieder M, Saeed HN, Shear NH, Shieh C, Straus S, Sukasem C, Sung C, Trubiano JA, Tsou S-Y, Ueta M, Volpi S, Wan C, Wang H, Wang Z-Q, Weintraub J, Whale C, Wheatley LM, Whyte-Croasdaile S, Williams KB, Wright G, Yeung SN, Zhou L, Chung W-H, Phillips EJ, Carleton BC. Corrigendum to 'SJS/TEN 2019: From science to translation' [J. Dermatol. Sci. 98/1 (2020) 2-12]. J Dermatol Sci 2021;104(2):146-147.
Gnanaguru G, Mackey A, Choi EY, Arta A, Rossato FA, Gero TW, Urquhart AJ, Scott DA, D'Amore PA, Ng YSE. Discovery of sterically-hindered phenol compounds with potent cytoprotective activities against ox-LDL-induced retinal pigment epithelial cell death as a potential pharmacotherapy. Free Radic Biol Med 2021;Abstract
Late-stage dry age-related macular degeneration (AMD) or geographic atrophy (GA) is an irreversible blinding condition characterized by degeneration of retinal pigment epithelium (RPE) and the associated photoreceptors. Clinical and genetic evidence supports a role for dysfunctional lipid processing and accumulation of harmful oxidized lipids in the pathogenesis of GA. Using oxidized low-density lipoprotein (ox-LDL)-induced RPE death assay, we screened and identified sterically-hindered phenol compounds with potent protective activities for RPE. The phenol-containing PPARγ agonist, troglitazone, protected against ox-LDL-induced RPE cell death, whereas other more potent PPARγ agonists did not protect RPE cells. Knockdown of PPARγ did not affect the protective activity of troglitazone in RPE, confirming the protective function is not due to the thiazolidine (TZD) group of troglitazone. Prototypical hindered phenol trolox and its analogs potently protected against ox-LDL-induced RPE cell death whereas potent antioxidants without the phenol group failed to protect RPE. Hindered phenols preserved lysosomal integrity against ox-LDL-induced damage and FITC-labeled trolox was localized to the lysosomes in RPE cells. Analogs of trolox inhibited reactive oxygen species (ROS) formation induced by ox-LDL uptake in a dose-dependent fashion and were effective at sub-micromolar concentrations. Treatment with trolox analog 2,2,5,7,8-pentamethyl-6-chromanol (PMC) significantly induced the expression of the lysosomal protein NPC-1 and reduced intracellular cholesterol level upon ox-LDL uptake. Our data indicate that the lysosomal-localized hindered phenols are uniquely potent in protecting the RPE against the toxic effects of ox-LDL, and may represent a novel pharmacotherapy to preserve the vision in patients with GA.
Guo X, Friedman DS, Repka MX, Collins ME. Visual acuity and refractive findings in children prescribed glasses from a school-based vision program. J AAPOS 2021;Abstract
PURPOSE: We report visual acuity improvement and refractive profiles in children prescribed glasses by a school-based vision program (SBVP) in Baltimore, Maryland. METHODS: In this cross-sectional analysis, pre-kindergarten through 8th grade students who failed vision screening underwent an eye examination. Students prescribed glasses are included. Visual acuity improvement was the difference between presenting and best-corrected visual acuity based on noncycloplegic manifest refraction. Clinically significant refractive error (CSRE) was defined as ≥0.75 D myopia, ≥2.00 D hyperopia without strabismus, ≥1.00 D hyperopia with esodeviation, or ≥1.50 D astigmatism AND presenting visual acuity ≤20/40 or ≥2-line difference with the better-seeing eye ≤20/30. Characteristics associated with greater visual acuity improvement were explored. RESULTS: Of the 4,972 students, mean age was 9.4 ± 2.7 years; 77% were black, and 18% were Hispanic. Myopia, hyperopia, astigmatism, and CSRE were found in 65%, 24%, 60%, and 46% students, respectively. In the better-seeing eyes, 70% gained ≥2 lines. Of students with CSRE, improvement of at least 5 lines in the worse-seeing eye increased from 30.9% in pre-kindergarten and kindergarten to 77.3% in 7th and 8th grade (Ptrend < 0.001). Students with CSRE had a higher rate of gaining at least 2 lines' improvement in their worse-seeing eyes compared with those without (98.7% vs 80.6%). Older students as well as blacks and Hispanics were more likely to have improvement of at least 2 lines. CONCLUSIONS: Most students prescribed glasses from our SBVP had clinically significant visual deficits corrected.
Tomita Y, Qiu C, Bull E, Allen W, Kotoda Y, Talukdar S, Smith LEH, Fu Z. Müller glial responses compensate for degenerating photoreceptors in retinitis pigmentosa. Exp Mol Med 2021;Abstract
Photoreceptor degeneration caused by genetic defects leads to retinitis pigmentosa, a rare disease typically diagnosed in adolescents and young adults. In most cases, rod loss occurs first, followed by cone loss as well as altered function in cells connected to photoreceptors directly or indirectly. There remains a gap in our understanding of retinal cellular responses to photoreceptor abnormalities. Here, we utilized single-cell transcriptomics to investigate cellular responses in each major retinal cell type in retinitis pigmentosa model (P23H) mice vs. wild-type littermate mice. We found a significant decrease in the expression of genes associated with phototransduction, the inner/outer segment, photoreceptor cell cilium, and photoreceptor development in both rod and cone clusters, in line with the structural changes seen with immunohistochemistry. Accompanying this loss was a significant decrease in the expression of genes involved in metabolic pathways and energy production in both rods and cones. We found that in the Müller glia/astrocyte cluster, there was a significant increase in gene expression in pathways involving photoreceptor maintenance, while concomitant decreases were observed in rods and cones. Additionally, the expression of genes involved in mitochondrial localization and transport was increased in the Müller glia/astrocyte cluster. The Müller glial compensatory increase in the expression of genes downregulated in photoreceptors suggests that Müller glia adapt their transcriptome to support photoreceptors and could be thought of as general therapeutic targets to protect against retinal degeneration.
Olafsson J, Lai X, Landsend ECS, Olafsson S, Parissi E, Utheim ØA, Raeder S, Badian RA, Lagali N, Dartt DA, Utheim TP. TheraPearl Eye Mask and Blephasteam for the treatment of meibomian gland dysfunction: a randomized, comparative clinical trial. Sci Rep 2021;11(1):22386.Abstract
Meibomian gland dysfunction (MGD) is the most common cause of dry eye disease (DED). In this study, we aimed to compare the effects of eyelid warming treatment using either TheraPearl Eye Mask (Bausch & Lomb Inc., New York, USA) or Blephasteam (Spectrum Thea Pharmaceuticals LTD, Macclesfield, UK) in a Norwegian population with mild to moderate MGD-related DED. An open label, randomized comparative trial with seventy patients (49 females, 21 males; mean age 53.6 years). Patients were randomly assigned to treatment with Blephasteam (n = 37) or TheraPearl (n = 33). All received a hyaluronic acid based artificial tear substitute (Hylo-Comod, Ursapharm, Saarbrücken, Germany). Patients were examined at baseline, and at three and six months initiation of treatment. Treatment efficacy was primarily evaluated by fluorescein breakup time (FBUT) and Ocular Surface Disease Index (OSDI) scores. Other outcome measures included ocular surface staining (OSS), Schirmer's test, and meibomian quality and expressibility. Baseline parameter values did not differ between the groups. After six months of treatment, Blephasteam improved FBUT by 3.9 s (p < 0.01) and OSDI by 13.7 (p < 0.01), TheraPearl improved FBUT by 2.6 s (p < 0.01) and OSDI by 12.6 (p < 0.01). No difference between treatments was detected at 6 months (p = 0.11 for FBUT and p = 0.71 for OSDI), nor were there differences in the other tested parameters between the treatment groups. Blephasteam and TheraPearl are equally effective in treating mild to moderate MGD in a Norwegian population after 6-months of treatment.Clinicaltrials.gov ID: NCT03318874; Protocol ID: 2014/1983; First registration: 24/10/2017.
Betzler BK, Gunasekeran DV, Kempen J, Smith JR, McCluskey P, Nguyen QD, Pavesio C, Gupta V, Agrawal R. The Historical Evolution of Ocular Tuberculosis: Past, Present, and Future. Ocul Immunol Inflamm 2021;:1-7.Abstract
Ocular involvement is a rare manifestation of tuberculosis. Four key issues historically faced by clinicians when diagnosing and treating ocular tuberculosis - diagnostic uncertainty, naturally heterogeneous presentations, limitations of existing laboratory diagnostic tools, and non-uniform treatment guidelines - continue to test today's physicians. Unparalleled scientific and clinical developments over the past century have greatly expanded the knowledge surrounding this challenging ophthalmic condition. Experience with large volumes of cases at tuberculosis-endemic centres has led to recent growth in knowledge and physician experience, perhaps more so in developing countries. Looking forward, the role of diverse new technologies, including artificial intelligence and proteomics, will advance ocular tuberculosis research. Efforts have been made to address the lack of standardized nomenclature, diagnostic uncertainty, and unvalidated, geographically variable treatment guidelines.
Kenyon KR. Comment on Cornea Classic Article: Kim JC and Tseng SCG: Transplantation of Preserved Amniotic Membrane for Surface Reconstruction in Severely Damaged Rabbit Corneas (Cornea 14: 473-484; 1995).". Cornea 2021;Abstract
ABSTRACT: Following identification of limbal stem cells, efforts have been devoted to restore and/or replace these essential progenitors of the corneal epithelium. Limbal stem cell deficiency, commonly a consequence of ocular chemical injury, results in clinically compromised vision consequent to corneal conjunctivalization. The insight of Kim and Tseng provided experimental proof of the concept that even in the presence of total limbal stem cell deficiency, amnion membrane overlay grafts can promote limbal recovery as a means of ocular surface reconstruction.

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